First off, thanks very much for taking the time to answer these questions; I know it is much appreciated by all of our members, some of whom know how busy you are!

Can you briefly explain for our readers how you came to be dealing with TMAU patients and your experience in this field?

I work in the largest centre in Europe looking after adults with inherited metabolic diseases.When I started here four years ago, we already looked after a handful of patients with TMAU.Soon after I arrived, Nigel Manning contacted me to ask if I would be happy if he suggested to GPs and other doctors who were sending diagnostic tests to him in Sheffield that they referred patients to us for specialist management.This made sense as we look after a number of other diseases which are treated with special diets and have excellent specialist metabolic dieticians in the Unit.The number of patients, and our experience, has grown steadily since then.

How many TMAU patients do you currently see?

Around 30.

Are you the only UK expert who sees referred patients on a daily basis?

I don’t see patients with TMAU on a daily basis, but I think we see many more adult patients than anyone else in the country.

If someone suspects they have TMAU can you outline the procedure they should take to get tested and be referred to yourself (or another consultant – if there are any?).

The best way to get a diagnosis is to send a urine test for TMA whilst you are eating a diet high in TMA and choline (we can give you advice on suitable foods to eat).If your GP is happy to arrange this for you (the urine needs to be collected in a special acidified bottle) then that is fine.If not, we are very happy to do the testing from here, but we do need a referral from your GP.

If the test comes back positive, then it should be possible to help your symptoms with a combination of various treatments including the low choline diet and antibiotics.This requires specialist input and we are happy to see patients from all over the country, but you will again need to be referred by your GP.

Do you currently have a waiting list to see patients and if so can people see you as a private patient?

We can normally offer patients an appointment within a week or two of having received the referral and it shouldn’t be necessary to see anyone privately.

Are there any figures on the number of people diagnosed with TMAU in the UK (and worldwide?)

Nigel Manning would be able to answer this better than me.

Most people who visit the tmau site are now aware of the urine test, Is it possible to ‘pass’ a TMAU urine test whilst still having the disorder?

Many patients with secondary TMAU have intermittent symptoms.If urine is taken at a time when there is no odour, then it might be negative for TMA.That is why we like to do diagnostic testing after a choline load.

Can you briefly outline the urine test and the resulting diagnosis from it?

I have outlined the testing procedure above.What they measure in the urine is the levels of TMA and TMAO.FMO3 converts TMA to TMAO so if you have normal FMO3 activity and take a choline load, the levels of TMA in the urine will not rise very much, but the TMAO will go up markedly.If the FMO3 enzyme is not working properly, then it will not be able to convert all the TMA to TMAO and the levels of both compounds will increase.

Can the diagnosis be done by means of a blood test?

No.Once the diagnosis has been made by a urine test, we sometimes send blood for genetic testing, but this can often be normal even in patients with strongly positive urine tests.

Is there any difference between the effectiveness of the different types of antibiotics for treating TMAU symptoms and how do they work?

The antibiotics are a pretty crude tool.We use them to reduce the levels of all the bacteria in the gut, not just the ones which produce TMA.This should lead to less TMA being produced and hence an improvement in symptoms.Over time, however, the bacteria will grow back.Using probiotics might encourage the non-TMA producing bacteria to grow back more strongly, perhaps keeping the TMA-producing bacteria in check.

When symptoms recur, another course of antibiotics can be given.The reason we rotate different antibiotics is so that the bacteria in the gut don’t become resistant to any one drug through constant exposure.They should all have similar effectiveness.

How often can you safely take the antibiotics?

We recommend giving antibiotics for two weeks at a time and prefer to leave at least 6 to 8 weeks between courses of antibiotics.

What is your take on the use of copper chlorophyllin, charcoal and champex in the treatment of TMAU symptoms? (I guess we’re asking about the general feedback you may have had from patients trying these, is there any scientific weight behind these products)

The idea is that these products can bind the TMA in the gut and prevent it from being absorbed into the body.Some people seem to find them useful, but not everyone does.They are probably worth a try.

Some people take probiotics and believe this may help with the symptoms, is this correct?

See above

Can people who think they may have TMAU follow a low choline diet before diagnosis or referral without any adverse side effects, or should they always consult a dietician first?

The low choline diet is quite restrictive.The main concern is that people will develop vitamin deficiencies, which is why we like to monitor them periodically in clinic.The diet is also quite complicated, and that is where expert dietetic advice can be valuable.

If someone has TMAU and follows the same strict diet can the levels of TMA change due to other factors? (Some people have mentioned that they think stress can make their symptoms worse)

Certainly there are factors, such as the menstrual cycle, which can affect symptoms, but we don’t understand why.

Why does it take, in some cases, many years for patients with primary TMAU to display any symptoms?

This is probably to do with how much FMO3 activity they have and how that is affected by other things such as hormonal factors.Many people become aware of their symptoms around the time of puberty.

That states “Heterozygotes (carriers) are asymptomatic”. Some people believe that being a carrier means you may exhibit transient TMAU symptoms; can you clarify this point for our readers?

I’m afraid this is one of the many things we don’t understand enough about.In most cases the parents of people with primary TMAU, who must be carriers, do not suffer any symptoms.On the other hand, people with secondary TMAU do sometimes have changes in their FMO3 genes.However, many people with the same changes don’t have any problems.

Does secondary Trimethylaminuria have any specific known causes and can antibiotic treatment prevent this from reoccurring?

Occasionally secondary TMAU may be caused by bacterial overgrowth in the gut (i.e. too many TMA producing bacteria).Sometimes this can be related to structural abnormalities of the bowel (so-called blind loop syndromes).In these cases antibiotic therapy may help control symptoms and surgery might also be an option.In the vast majority of cases, however, the gut is entirely normal.

My 8 y.o. daughter has mild TMAU, so I attend our metabolic unit, and we made dietary changes. The odour fluctuates from non-existent some days, mild most days, and then a few days of strong. But I can't relate it to her diet. Our first test (after eating fish the night before!) showed TMA 14.3, ratio 93:7, then I cut out the forbidden foods and the next test was TMA 27.8, ratio 86:14!

I still wonder is there something else going on, because the diet doesn't seem to have an effect. I even tried giving her fish every day for a week, then eggs every day another week, but I can't relate the pattern of symptoms to her food at all.

Should I request a referral to an endocrinologist maybe?

We know that in secondary TMAU the FMO3 enzyme doesn't work properly even though there is no obvious genetic problem with it, so there must be other factors which can effect the enzyme.In adult women, symptoms can be worse around their periods, so hormones probably are important.Nonetheless, the dietary intake and conversion of choline to TMA in the gut should be the main things which determine when there is odour.I would suggest talking to your metabolic consultant to see what they think.

Do you consider TMAU to be a disability?

TMAU is certainly disabling and can have a major effect on people’s lives causing distress, depression and social isolation.

Are you aware on any significant ongoing or future research / studies in relation to TMAU?

We are certainly not involved in any research at the present time.

Is it possible, some day, to cure TMAU?

In principle the disease could be cured by liver transplantation.At the moment the risks of this procedure would far outweigh the benefits, but one day a stem cell treatment might become available.Gene therapy would also be an option, but I think that it is a long way off.

Finally do you have any other advice or encouragement you can give to our readers who suffer from TMAU?

I think that the good news is that the vast majority of patients with TMAU do get real benefits from treatment.Over time most people find a combination of diet, antibiotics, probiotics and other things (copper chlorophyllin, riboflavin) which work for them.Although we can’t cure the disease, treatment does allow people to get control over their symptoms which in turn gives them more confidence and allows them to do things that they previously found difficult and distressing.

First off, thanks very much for taking the time to answer these questions; I know it is much appreciated by all of our members, some of whom know how busy you are!

Can you briefly explain for our readers how you came to be dealing with TMAU patients and your experience in this field?

I work in the largest centre in Europe looking after adults with inherited metabolic diseases.When I started here four years ago, we already looked after a handful of patients with TMAU.Soon after I arrived, Nigel Manning contacted me to ask if I would be happy if he suggested to GPs and other doctors who were sending diagnostic tests to him in Sheffield that they referred patients to us for specialist management.This made sense as we look after a number of other diseases which are treated with special diets and have excellent specialist metabolic dieticians in the Unit.The number of patients, and our experience, has grown steadily since then.

How many TMAU patients do you currently see?

Around 30.

Are you the only UK expert who sees referred patients on a daily basis?

I don’t see patients with TMAU on a daily basis, but I think we see many more adult patients than anyone else in the country.

If someone suspects they have TMAU can you outline the procedure they should take to get tested and be referred to yourself (or another consultant – if there are any?).

The best way to get a diagnosis is to send a urine test for TMA whilst you are eating a diet high in TMA and choline (we can give you advice on suitable foods to eat).If your GP is happy to arrange this for you (the urine needs to be collected in a special acidified bottle) then that is fine.If not, we are very happy to do the testing from here, but we do need a referral from your GP.

If the test comes back positive, then it should be possible to help your symptoms with a combination of various treatments including the low choline diet and antibiotics.This requires specialist input and we are happy to see patients from all over the country, but you will again need to be referred by your GP.

Do you currently have a waiting list to see patients and if so can people see you as a private patient?

We can normally offer patients an appointment within a week or two of having received the referral and it shouldn’t be necessary to see anyone privately.

Are there any figures on the number of people diagnosed with TMAU in the UK (and worldwide?)

Nigel Manning would be able to answer this better than me.

Most people who visit the tmau site are now aware of the urine test, Is it possible to ‘pass’ a TMAU urine test whilst still having the disorder?

Many patients with secondary TMAU have intermittent symptoms.If urine is taken at a time when there is no odour, then it might be negative for TMA.That is why we like to do diagnostic testing after a choline load.

Can you briefly outline the urine test and the resulting diagnosis from it?

I have outlined the testing procedure above.What they measure in the urine is the levels of TMA and TMAO.FMO3 converts TMA to TMAO so if you have normal FMO3 activity and take a choline load, the levels of TMA in the urine will not rise very much, but the TMAO will go up markedly.If the FMO3 enzyme is not working properly, then it will not be able to convert all the TMA to TMAO and the levels of both compounds will increase.

Can the diagnosis be done by means of a blood test?

No.Once the diagnosis has been made by a urine test, we sometimes send blood for genetic testing, but this can often be normal even in patients with strongly positive urine tests.

Is there any difference between the effectiveness of the different types of antibiotics for treating TMAU symptoms and how do they work?

The antibiotics are a pretty crude tool.We use them to reduce the levels of all the bacteria in the gut, not just the ones which produce TMA.This should lead to less TMA being produced and hence an improvement in symptoms.Over time, however, the bacteria will grow back.Using probiotics might encourage the non-TMA producing bacteria to grow back more strongly, perhaps keeping the TMA-producing bacteria in check.

When symptoms recur, another course of antibiotics can be given.The reason we rotate different antibiotics is so that the bacteria in the gut don’t become resistant to any one drug through constant exposure.They should all have similar effectiveness.

How often can you safely take the antibiotics?

We recommend giving antibiotics for two weeks at a time and prefer to leave at least 6 to 8 weeks between courses of antibiotics.

What is your take on the use of copper chlorophyllin, charcoal and champex in the treatment of TMAU symptoms? (I guess we’re asking about the general feedback you may have had from patients trying these, is there any scientific weight behind these products)

The idea is that these products can bind the TMA in the gut and prevent it from being absorbed into the body.Some people seem to find them useful, but not everyone does.They are probably worth a try.

Some people take probiotics and believe this may help with the symptoms, is this correct?

See above

Can people who think they may have TMAU follow a low choline diet before diagnosis or referral without any adverse side effects, or should they always consult a dietician first?

The low choline diet is quite restrictive.The main concern is that people will develop vitamin deficiencies, which is why we like to monitor them periodically in clinic.The diet is also quite complicated, and that is where expert dietetic advice can be valuable.

If someone has TMAU and follows the same strict diet can the levels of TMA change due to other factors? (Some people have mentioned that they think stress can make their symptoms worse)

Certainly there are factors, such as the menstrual cycle, which can affect symptoms, but we don’t understand why.

Why does it take, in some cases, many years for patients with primary TMAU to display any symptoms?

This is probably to do with how much FMO3 activity they have and how that is affected by other things such as hormonal factors.Many people become aware of their symptoms around the time of puberty.

That states “Heterozygotes (carriers) are asymptomatic”. Some people believe that being a carrier means you may exhibit transient TMAU symptoms; can you clarify this point for our readers?

I’m afraid this is one of the many things we don’t understand enough about.In most cases the parents of people with primary TMAU, who must be carriers, do not suffer any symptoms.On the other hand, people with secondary TMAU do sometimes have changes in their FMO3 genes.However, many people with the same changes don’t have any problems.

Does secondary Trimethylaminuria have any specific known causes and can antibiotic treatment prevent this from reoccurring?

Occasionally secondary TMAU may be caused by bacterial overgrowth in the gut (i.e. too many TMA producing bacteria).Sometimes this can be related to structural abnormalities of the bowel (so-called blind loop syndromes).In these cases antibiotic therapy may help control symptoms and surgery might also be an option.In the vast majority of cases, however, the gut is entirely normal.

My 8 y.o. daughter has mild TMAU, so I attend our metabolic unit, and we made dietary changes. The odour fluctuates from non-existent some days, mild most days, and then a few days of strong. But I can't relate it to her diet. Our first test (after eating fish the night before!) showed TMA 14.3, ratio 93:7, then I cut out the forbidden foods and the next test was TMA 27.8, ratio 86:14!

I still wonder is there something else going on, because the diet doesn't seem to have an effect. I even tried giving her fish every day for a week, then eggs every day another week, but I can't relate the pattern of symptoms to her food at all.

Should I request a referral to an endocrinologist maybe?

We know that in secondary TMAU the FMO3 enzyme doesn't work properly even though there is no obvious genetic problem with it, so there must be other factors which can effect the enzyme.In adult women, symptoms can be worse around their periods, so hormones probably are important.Nonetheless, the dietary intake and conversion of choline to TMA in the gut should be the main things which determine when there is odour.I would suggest talking to your metabolic consultant to see what they think.

Do you consider TMAU to be a disability?

TMAU is certainly disabling and can have a major effect on people’s lives causing distress, depression and social isolation.

Are you aware on any significant ongoing or future research / studies in relation to TMAU?

We are certainly not involved in any research at the present time.

Is it possible, some day, to cure TMAU?

In principle the disease could be cured by liver transplantation.At the moment the risks of this procedure would far outweigh the benefits, but one day a stem cell treatment might become available.Gene therapy would also be an option, but I think that it is a long way off.

Finally do you have any other advice or encouragement you can give to our readers who suffer from TMAU?

I think that the good news is that the vast majority of patients with TMAU do get real benefits from treatment.Over time most people find a combination of diet, antibiotics, probiotics and other things (copper chlorophyllin, riboflavin) which work for them.Although we can’t cure the disease, treatment does allow people to get control over their symptoms which in turn gives them more confidence and allows them to do things that they previously found difficult and distressing.